Intravenous (iv) infusion of allogeneic spleen cells into mice that subsequently are given skin allografts causes the prolonged survival of these grafts if they are from donors belonging to the same strain as the donors of the iv infused spleen cells. This capacity for iv infused allogeneic spleen cells to cause alloantigen-specific prolongation of graft survival may be an experimental manifestation of a similar phenomenon documented clinically. The chance for long-term survival of human organ grafts appears to be improved if the recipient of the organ graft has received one or more blood transfusions prior to grafting. The long-term goal of the proposed research is to maximize the potential that iv infusion of allogeneic cells may have to improve the survival of organ and tissue grafts. To achieve that goal, the immunological basis must be known for the beneficial effect on allograft survival produced by allogeneic cells infused iv. The specific aims of the experiments described in this proposal are (1) to determine whether prolonged survival of skin grafts expressing the same minor histocompatibility antigens as spleen cells previously infused iv is mediated by veto cells in the infused population or by cells or serum factors generated by the recipient in response to iv cell infusion, (2) to determine whether infused allogeneic spleen cells prolong allograft survival by directly or indirectly suppressing the activity of the effectors of allograft rejection or the generation of those effectors, and (3) to investigate the effect that iv infused spleen cells have on the acquisition or expression of immunological memory for minor histocompatibility antigens on the infused cells.